GRHL1

protein-coding

grainyhead like transcription factor 1

Gene summary

This gene encodes a member of the grainyhead family of transcription factors. The encoded protein can exist as a homodimer or can form heterodimers with sister-of-mammalian grainyhead or brother-of-mammalian grainyhead. This protein functions as a transcription factor during development. [provided by RefSeq, Jun 2009]

Previous symbols:

TFCP2L2

MANE transcript

NM_198182.3

Inheritance

—

ClinVar variants

U:76B:2

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.24

Max pathogenic AF

—

Genomic locus

chr2:9,951,693-10,002,277

External References & Databases

Ensembl (ENSG00000134317)

Transcript & Mutation Effects

hg38 • Region Span ~50.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GRHL1 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 65

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_198182.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar		1 clinvar	5
missense			70 clinvar	1 clinvar		71
nonsense			1 clinvar			1
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	76	1	1	78

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 18 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_198182.3	RefSeq	NP_937825.2	16	MANE Select
ENST00000324907.14	Ensembl	ENSP00000324693.9	16	MANE Select
ENST00000405379.6	Ensembl	ENSP00000384209.3	12	Standard
ENST00000405379.7	Ensembl	ENSP00000384209.3	12	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
grhl1	Danio rerio	Structure: neuromast hair cell Quality: decreased amount abnormal

Gene / Model

Organism

Observed Phenotype

grhl1

Danio rerio

Structure: neuromast hair cell

Quality: decreased amount

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Regulation of lipid metabolism by Peroxisome proliferator-activated receptor alpha (PPARalpha)

Biological Process

desmosome organization
regulation of transcription by RNA polymerase II
epidermis development
regulation of lipid metabolic process
regulation of keratinocyte differentiation

Molecular Function

RNA polymerase II proximal promoter sequence-specific DNA binding
DNA-binding transcription factor activity, RNA polymerase II-specific
DNA-binding transcription activator activity, RNA polymerase II-specific
DNA-binding transcription factor activity
protein binding

Cellular Component

nucleus
nucleoplasm
Golgi apparatus
cytosol
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000324907
Coding exons: 16
Length: 57071
Individuals with no LoFs: 125734
Homozygous LoFs: 0
Heterozygous LoFs: 14
Defined: 125748
p: 0.0000557

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.68	258	346	0.745	0.0000190	4078
Missense (PolyPhen)		97	146.02	0.66431		1726
Synonymous	0.539	127	135	0.941	0.00000809	1153
Loss of Function	4.11	8	33.7	0.237	0.00000188	394

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00019	0.00018	rare
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0.000098	0.000098	rare
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Transcription factor involved in epithelial development. Binds directly to the consensus DNA sequence 5'-AACCGGTT-3' (PubMed:12175488, PubMed:18288204, PubMed:29309642). Important regulator of DSG1 in the context of hair anchorage and epidermal differentiation, participates in the maintenance of the skin barrier. There is no genetic interaction with GRHL3, no functional cooperativity due to diverse target gene selectivity during epithelia development (By similarity). {ECO:0000250|UniProtKB:Q921D9, ECO:0000269|PubMed:12175488, ECO:0000269|PubMed:18288204, ECO:0000269|PubMed:29309642}.; FUNCTION: Isoform 2: May function as a repressor in tissues where both isoform 1 and isoform 2 are expressed. {ECO:0000269|PubMed:12175488}.;

Recessive Scores

pRec: 0.201

Intolerance Scores

LoFtool: 0.453
RVIS EVS: -0.11
RVIS percentile EVS: 45.26

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Indispensability pred.: E
Indispensability score: 0.901

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium